GPR61 Membrane Protein Introduction

Introduction of GPR61

Probable G-protein coupled receptor 61, also known as Biogenic amine receptor-like G-protein coupled receptor, is a protein that belongs to the G-protein coupled receptor 1 family which is encoded by the GPR61 gene. As a member of G protein-coupled receptors, GPR61 contains 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. In the past years, GPR61 has been extensively studied for its functions and applications. Numerous studies have suggested that GPR61 is most closely related to biogenic amine receptors.

Function of GPR61 Membrane Protein

G protein-coupled receptors (GPCRs) constitute the largest membrane protein family in humans that detect various extracellular stimuli including odor, photons, nutrients, hormones, and neurotransmitters. They are the therapeutic targets for nearly a third of clinically marketed drugs. In the past years, studies have suggested that GPCRs play diverse physiological roles and convey their effects in a highly specific manner. As a member of the so-called orphan receptors, GPR61 is a 49 kDa GPCR that belongs to orphan receptors class A. It shares some degree of sequence similarity (28-31%) with certain histamine, adrenergic, serotonin, and dopamine receptors 2. What’s more, GPR61 has been reported to be broadly expressed in the brain, including in the cortex, hippocampus, thalamus, hypothalamus, and midbrain. Most importantly, GPR61 has a phenylalanine residue in the sixth transmembrane domain, which is conserved in many biogenic amine receptors. This phenylalanine residue is considered to interact with the aromatic ring of biogenic amine ligands.

Fig.1 Schematic drawing depicting the 7 helices and the different pathways upon G protein coupling. (Veulens, 2009)

Application of GPR61 Membrane Protein in Literature

1. Kozielewicz P., et.al. N-glycosylation and expression in human tissues of the orphan GPR61 receptor. FEBS open bio. 2017, 7(12):1982-93. PubMed ID: 29226084
   
   

   This article suggests that GPR61 protein is subject to post-translational modification and is expressed in immune cell subsets and the hippocampus which will help guide studies to investigate the function of GPR61.

2. Oishi A., et.al. Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT 2 receptor reciprocally modulate their signaling functions. Scientific reports. 2017, 7(1):8990. PubMed ID: 28827538
   
   

   This article suggests that GPR61 is unable to bind melatonin, but show a reciprocal regulatory interaction with MT2 receptors.

3. Pandey K., et.al. Heifers express G-protein coupled receptor 61 in anterior pituitary gonadotrophs in a stage-dependent manner. Animal reproduction science. 2017, 181:93-102. PubMed ID: 28433506
   
   

   This article aims to verify the assumption that GPR61 colocalizes with GnRHR in the plasma membrane of gonadotroph and is expressed at specific times of the reproductive cycle. It suggests that GPR61 colocalizes with GnRHR in the plasma membrane of gonadotrophs, and its expression changes stage-dependently in the bovine anterior pituitary gland.

4. Nambu H., et.al. Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor. Life sciences. 2011, 89(21-22):765-72. PubMed ID: 21971119
   
   

   This article aims to elucidate the importance of GPR61 in metabolism by characterization of GPR61-deficient mice. Research results show that GPR61-deficient mice exhibited obesity associated with hyperphagia. It indicates that GPR61 is involved in the regulation of food intake and body weight, and may be of importance when considering GPR61 as a therapeutic target for obesity or eating disorders.

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Reference

1. Veulens, et.al. (2009). Protein-coupled receptors as targets for drug design. Biotecnol April. 26, 24-33.

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